7NSZ

Drosophila PGRP-LB Y78F mutant

これはPDB形式変換不可エントリーです。

7NSZ の概要

• エントリーDOI: 10.2210/pdb7nsz/pdb
• 分子名称: Isoform A of Peptidoglycan-recognition protein LB, ZINC ION, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: peptidoglycan recognition protein, pgrp, pgrp-lb, drosophila, immune system
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24097.73

構造登録者

Orlans, J.,Aller, P.,Da Silva, P. (登録日: 2021-03-08, 公開日: 2021-05-19, 最終更新日: 2024-01-31)

主引用文献

Orlans, J.,Vincent-Monegat, C.,Rahioui, I.,Sivignon, C.,Butryn, A.,Soulere, L.,Zaidman-Remy, A.,Orville, A.M.,Heddi, A.,Aller, P.,Da Silva, P.
PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction.
Int J Mol Sci, 22:-, 2021

PubMed Abstract: Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving -2,6-diaminopimelic (-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of PGRP-LB towards various PGN substrates to understand their specificity and role in immunity. We show that these isoforms have similar activity towards the different compounds. To analyze the mechanism of the amidase activity, we performed site directed mutagenesis and solved the X-ray structures of wild-type PGRP-LB and its mutants, with one of these structures presenting a protein complexed with the tracheal cytotoxin (TCT), a muropeptide derived from the PGN. Only the Y78F mutation abolished the PGN cleavage while other mutations reduced the activity solely. Together, our findings suggest the dynamic role of the residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn.

PubMed: 34066955
DOI: 10.3390/ijms22094957

実験手法

X-RAY DIFFRACTION (1.3 Å)